The development of oral rehydration therapy (ORT) for acute diarrheal diseases of infancy and childhood has significantly reduced related morbidity and mortality, particularly in less developed countries where it constitutes the primary mode of therapy.
Oral rehydration solutions (ORS) used in ORT.Iadd., and compositions for prevention of dehydration or maintenance of hydration, .Iaddend.generally consist of a mixture of electrolytes and a carbohydrate component such as glucose or sucrose. The American Academy of Pediatrics recommends glucose at 2.0 to 2.5% by weight, potassium at 20 mEq/L, .Iadd.20%-30% of .Iaddend.anions as ..chloride and as.!. base (acetate, lactate, citrate, or bicarbonate .Iadd.and the remainder as chloride.Iaddend.), sodium at 75 to 90 mEq/L for acute dehydration and sodium at 40 to 60 mEq/L for the prevention of dehydration or maintenance of hydration (1985, Pediatrics, 75:358). The World Health Organization (WHO)/UNICEF currently recommends that oral rehydration solution contains 90 mEq sodium/liter, 20 mEq potassium/liter, 80 mEq Cl/liter, 30 mEq citrate/liter or 30 mEq bicarbonate/liter and glucose 110 mmol/liter. The WHO formulation has been shown to decrease morbidity and mortality in acute diarrheal disease but the magnitude of diarrhea in terms of volume and frequency of stools and the duration of the illness is not reduced.
Substitution of other carbohydrates for glucose in WHO-type formulations has been investigated. Lebenthal, et al., J. Pediatrics., 103:29-34 (1983) studied the effect of three corn syrup sugars (dextrins) containing glucose polymers of varying lengths having dextrose equivalents of 10, 15 and 24.Iadd., .Iaddend.and determined they were ..suitable as the sole carbohydrate source in ORT.!. .Iadd.digestible and clinically tolerated in diarrhea of infancy.Iaddend.. It has also been established that ORS in which rice and other food sources of starch are substituted for glucose are effective as reported by Carpenter, et al., New England Journal of Medicine, 319:1346-1348 (1988). In particular, ..rice-based.!. oral rehydration solutions .Iadd.made from whole rice .Iaddend.have been found to be effective as reported in the following publications.
Patra, et al Archives of Disease in Childhood, 57:910-912 (1982), "Is Oral Rice Electrolyte Solution Superior to Glucose Electrolyte Solution in Infantile Diarrhoea?" PA1 Molla, et al The Lancet, 1317-1319 (1982), "Rice-Powder Electrolyte Solution as Oral Therapy in Diarrhoea Due to Vibrio Cholerae and Escherichia Coli". PA1 El Mougi, et al Journal of Pediatric Gastroenterology and Nutrition, 7:572-576 (1988), "Controlled Clinical Trial on the Efficacy of Rice Powder-Based Oral Rehydration Solution on the Outcome of Acute Diarrhea in Infants". PA1 Molla, et al Journal of Gastroenterology and Nutrition, 8:81-84 (1989), "Turning Off The Diarrhea: The Role of Food and ORS". PA1 Patra, et al supra.--Sufficient powdered rice (prepared by popping unhusked rice on heated sand) was dissolved in rehydration fluid before use to make a 5% ORS. PA1 Molla, et al. (1982) supra.--Rice powder was first dissolved in several hundred milliliters of water and boiled for 1-2 minutes to make a uniform solution and then electrolytes added to make a 3% ORS. PA1 El Mougi, et al supra.--Sufficient rice powder was dissolved in 200 ml of hot water and cooked for 10 minutes until a gel formed to provide a semi-liquid 5% ORS. PA1 Molla, et al (1989) supra.--Sufficient rice flour was boiled in 1.1 liters of water for 5 to 7 minutes forming a homogeneous solution which was mixed with electrolytes to make a 4.5% ORS.
The ..rice-based.!. ORS .Iadd.made from whole rice .Iaddend.of the foregoing references contained from 3 to 5% rice and had electrolyte levels corresponding to conventional WHO ..formations.!. .Iadd.formulations.Iaddend.. They were prepared as follows.
One problem associated with the use of prior art ..rice-based.!. ORS .Iadd.made from whole rice .Iaddend.is that they must be prepared shortly before use because they are not sterile. Another problem with prior art ..rice.!. ORS .Iadd.made from whole rice .Iaddend.relates to the relative insolubility of rice flour which prevents preparation of pharmaceutically elegant crystal (water) clear ORS.
A primary object of the invention is to provide a stable ready-to-use ORS .Iadd.and a composition for prevention of dehydration or maintenance of hydration .Iaddend.wherein the carbohydrate component is rice dextrin.
Still another object of the invention is to provide an improved ..rice based.!. ORS .Iadd.and a composition for prevention of dehydration or maintenance of hydration .Iaddend.which results in lower stool output and a better water and potassium balance during the rehydration period.
.Iadd.Unless specifically noted otherwise, the term ORS refers to oral rehydration solutions as well as to solutions for the prevention of dehydration and maintenance of hydration..Iaddend.